The goal of this research is to use the cyclotron-produced short-lived radionuclide nitrogen-13 to study the in vivo metabolism of labeled L-amino acids and ammonia in murine tumors which are sensitive or resistant to glutaminase or asparaginase therapy. It is necessary to determine the specific amino acid requirements of a tumor as well as to understand amino acid metabolism to develop a rationale for treatment of tumors with amino acid-depleting enzymes and amino acid analogs. The metabolites of these N-13 labeled radiopharmaceuticals in blood and tumor homogenates will be determined using reverse phase and ion exchange chromatographic analyses. Metabolite determinations will be performed in animals that are untreated or treated with glutaminase, asparaginase or amino acid antagonists (MSO, DON or DONV). The results of this study will not only provide basic information about amino acid metabolism of tumors, but these positronemitting N-13 radiopharmaceuticals may be useful in diagnostic imaging to determine which tumors may be amenable to specific amino acid-depleting enzyme therapy. Metabolic fate studies have been performed on blood and tumor homogenates 5 minutes after either N-13 ammonia or L-(amide-N-13) glutamine administration in untreated glutaminase sensitive and resistant tumor-bearing mice. For both agents only 0.7% of the label recovered in both tumors was in protein and nucleic acid. The major fate of the N-13 label in either tumor after either N-13 ammonia or glutamine administration is as N-13 urea. There is much more N-13 present in the tumors as urea than the residual blood of the tumors, suggesting endogenous production of urea or active transport of urea by the tumors. There is no known precedent for the latter. The rate of turnover of both the ammonia and glutamine pools appears to be more rapid in the glutaminaseresistant tumor than the sensitive tumor.